Hindawi Publishing Corporation

Gastroenterology Research and Practice

Volume 2011, Article ID 857949, 9 pages
doi:10.1155/2011/857949

Review Article
Enteral Nutrition and Acute Pancreatitis: A Review

B. W. M. Spanier,1 M. J. Bruno,2 and E. M. H. Mathus-Vliegen3

1 Department of Gastroenterology and Hepatology, Rijnstate Hospital, P.O. Box 9555, 6800 TA Arnhem, The Netherlands
2 Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, 3000 CA Rotterdam, The Netherlands
3 Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam,

1105 AZ Amsterdam, The Netherlands

Correspondence should be addressed to B. W. M. Spanier, mspanier@alysis.nl

Received 12 May 2010; Accepted 22 June 2010

Academic Editor: Rémy Meier

Copyright © 2011 B. W. M. Spanier et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.

Introduction. In patients with acute pancreatitis (AP), nutritional support is required if normal food cannot be tolerated within
several days. Enteral nutrition is preferred over parenteral nutrition. We reviewed the literature about enteral nutrition in AP.
Methods. A MEDLINE search of the English language literature between 1999–2009. Results. Nasogastric tube feeding appears to
be safe and well tolerated in the majority of patients with severe AP, rendering the concept of pancreatic rest less probable. Enteral
nutrition has a beneficial influence on the outcome of AP and should probably be initiated as early as possible (within 48 hours).
Supplementation of enteral formulas with glutamine or prebiotics and probiotics cannot routinely be recommended. Conclusions.
Nutrition therapy in patients with AP emerged from supportive adjunctive therapy to a proactive primary intervention. Large
multicentre studies are needed to confirm the safety and effectiveness of nasogastric feeding and to investigate the role of early
nutrition support.

1. Introduction
Acute pancreatitis (AP) ranges from a mild and self-
limiting disease (80%), which usually resolves spontaneously
within days, to a rapidly progressive fulminant illness with
significant morbidity and mortality [1, 2]. The two most
common etiological factors, representing more than 80% of
cases, are gallstones and alcohol abuse [1, 3].
The clinical course of an attack of AP varies from
a short period of hospitalization with supportive care to
prolonged hospitalization and admittance to an Intensive
Care Unit (ICU) because of the development of systemic
inflammatory response syndrome (SIRS), multiorgan failure
(MOF), and septic complications. Overall, in about 15%
to 20% of patients, AP progresses to a severe illness with
a prolonged disease course. These severely ill patients may
develop organ failure and/or local complications such as
pancreatic necrosis. In patients with necrotizing pancreatitis,
the mortality is close to 17%, with a mortality of 12% in the
case of sterile necrosis and up to 30% in infected necrosis [1].
Usually, the initial treatment of AP consists of a nil
per os (NPO) regimen and the administration of analgesics
and ample intravenous fluids [1, 2, 4]. The rationale for a
period without food intake is the assumption that pancreatic
stimulation by enteral feeding may aggravate pancreatic
inflammation. The validity of this concept of “pancreatic
rest” is heavily debated [5–7]. Moreover, many patients
are anorectic and may suffer increasing pain sensations
when eating and ileus-related nausea and vomiting. The
resumption of oral feeding depends on the improvement
of abdominal pain, absence of nausea and vomiting, and
return of appetite. Nutritional support is required in those
patients who cannot tolerate normal food within several days
[1, 4, 8, 9].
To date, there is a substantial scientific proof that enteral
feeding is superior to total parenteral nutrition (TPN) [5, 6,
10–15]. The beneficial effects of enteral feeding on mucosal
integrity and the prevention of bacterial overgrowth may well
explain the superiority of enteral feeding over TPN [16, 17].
Enteral feeding significantly reduces the risk of infections,
lowers the need for surgical interventions, and reduces
the length of hospital stay [5, 6, 10–12, 15, 18]. Recently,
Petrov and coworkers concluded in their meta-analysis that
mortality is significantly reduced when patients with a
2 Gastroenterology Research and Practice
predicted severe AP are fed enterally [14]. Importantly, this
reduction of mortality in patients with a severe AP may also
be related to the timing of the start of nutrition, within 48
hours after admission [13]. Whenever enteral nutrition is
initiated, issues such as the ideal composition, timing, and
route of delivery should be considered, as they may all impact
on the outcome of AP. Patients who are unable to tolerate
enteral nutrition need to be managed with TPN until such
time that they can tolerate enteral feeding [9]. In this review
an update is given about several aspects of enteral nutrition
in mild and severe AP.
2. Pancreatic Rest and Pancreatic Secretion
Efforts to keep up with the increased energy demands in the
case of AP are thwarted by the adage to put the pancreas
at rest and the avoidance of pancreatic stimulation via
gut luminal nutrition. As mentioned in the introduction,
this adage merits reconsideration. The concept of “putting
the pancreatic to rest” assumes that pancreatic rest pro-
motes healing, decreases pain, and reduces secretion and
leakage of pancreatic juices in pancreas parenchyma and
peripancreatic tissue [19]. The concept of pancreatic rest
originates from the classic work of Ragins et al. based
on a canine model [20]. They demonstrated that jejunal
feeding did not stimulate pancreatic secretion as opposed
to intragastric or intraduodenal feeding. However, this
concept of “putting the pancreas to rest” disregards the
persistence of basal pancreatic exocrine secretion. Of the
three components of pancreas secretion (protein enzymes,
fluid volume, and bicarbonate), protein enzyme output is
responsible for autodigestion of the gland and perpetuation
of the inflammatory process [19]. Suppression of protein
enzyme output alone with continued bicarbonate and fluid
volume output may therefore be adequate in putting the
pancreas to rest.
2.1. Physiology of Pancreatic Secretion. Basal enzyme secre-
tion is 20% of maximal enzyme secretion and is regulated
by cholinergic and cholocystokinin (CCK)-mediated mech-
anisms. Feeding by mouth increases pancreas secretion by
involving three levels of stimulation via three interrelated
phases: the cephalic, gastric, and intestinal phase [21, 22].
The cephalic phase is mediated through direct cholinergic
stimulation by the vagus nerve on pancreatic acinar cells. The
vagus also acts indirectly by stimulating gastrin release from
the antrum and vasoactive intestinal peptide (VIP) release
from the small intestine. The gastric phase of pancreatic
secretion has not been fully elucidated. Gastrin affects pan-
creatic secretion by two mechanisms: gastric acid secretion,
resulting in secretin secretion when a low pH reaches the
duodenum and a direct effect of gastrin on acinar cells
to produce an enzyme-rich secretion. The intestinal phase
accounts for the majority of postprandial exocrine pancreatic
secretory output and is orchestrated by multiple mediators:
vagus nerve, CCK and VIP, a secretin-like hormone, and
cholinergic enteropancreatic reflexes.
Human pancreatic enzyme output reaches maximal rates
following a mixed meal of 20 kcal/kg body weight [23, 24].
The duration of the response increases with greater caloric
load. The pancreatic response is also influenced by the
physical properties of the meal: mixed solid-liquid meals
induce a higher response than liquid or homogenized meals
with a similar energy content. In both instances, the rate
of gastric emptying and thus duodenal delivery of nutrients
are the key factors which determine the duration of the
pancreatic secretion. Proportion of fat, carbohydrate, and
protein contents within a meal also influence the duration
and enzyme composition of the pancreatic response in
humans.
2.2. Pancreatic Secretion with Total Enteral Nutrition. Recent
human studies show that all common forms of EN to some
extent stimulate the pancreas and only parenteral nutri-
tion avoids pancreatic stimulation [25, 26]. Considerable
evidence exists that the degree to which the pancreas is
stimulated by enteral nutrition (EN) is determined by the
site in the gastrointestinal tract at which feedings are infused.
Feeding infused into the jejunum beyond the ligament of
Treitz may bypass the cephalic, gastric, and intestinal phase of
stimulation of pancreatic secretion, is less likely to stimulate
CCK and secretin, and may stimulate inhibiting polypeptides
[27–29]. It has been demonstrated in human studies during
jejunal feeding, that pancreatic enzyme output increased
significantly over basal levels when it was delivered at
the ligament of Treitz, whereas there was no significant
increase during more distal jejunal feeding, 60 cm beyond
the ligament of Treitz [30]. A more recent study in healthy
volunteers showed that EN can be given without stimulating
pancreatic trypsin secretion provided that it is delivered into
the mid-distal jejunum [31]. Feeding from 20 to 120 cm
beyond the ligament of Treitz had no stimulatory effect.
Also the composition of the infused feeds is important.
There is considerable evidence to support an added benefit of
elemental formulae for putting the pancreas to rest compared
to standard formulae with intact protein or blenderized diets
[19]. Elemental diets cause less stimulation than standard
formulas, because of their low fat content, the presence of
free aminoacids instead of intact proteins which bind to free
trypsin in the gut, causing trypsin levels to fall, and less acid
production from the stomach.
2.3. Outcomes of Pancreatic Rest. Whether pancreatic rest has
a role to play in patients with severe AP is still uncertain, as
no well-powered randomized, prospective studies have been
carried out to address this specific question [6]. Whether
pancreatic rest is at all needed is questioned by the results
of several studies comparing nasogastric with nasojejunal
feeding in severe AP, as nastrogastric feeding appears to be
safe and well tolerated [32, 33].
Putting the pancreas to rest is based on the assumption
that the inflamed and/or necrotic pancreas is still a secretor
of activated enzymes once stimulated. Animal studies have
shown that pancreatic exocrine secretion in experimental AP
in response to CCK stimulation is suppressed [34]. A small
Gastroenterology Research and Practice 3

prospective study showed pancreatic exocrine insufficiency chemistry, gastrointestinal symptoms, complications, and
to be common in patients recovering from severe AP; its interventions. The orally fed group had a significant 2-
severity correlated with the extent of pancreatic necrosis [35]. day shorter length of hospital stay without differences in
Another study demonstrated that trypsin secretion in AP recurrent attacks of pancreatitis in a follow-up of 3 months.
patients, especially with necrotizing AP, is significantly sup-
pressed compared to healthy individuals. However, despite
these low rates of luminal secretion, the rate of appearance of 4. Modifications of Enteral Nutrition
newly synthesized trypsin was unchanged [36]. Thus, a more
4.1. Standard Composition: Elemental, Semielemental, or
likely alternative explanation for the absence of exacerbation
Polymeric Formulas. Few studies to date compare the results
of the disease during EN is that the pancreas becomes less
of feeding elemental, semielemental, and polymeric diets to
responsive to EN stimulation during an attack of AP and
patients with AP [7, 15]. Elemental formula are completely
that the secretory response to EN is suppressed to basal rates
predigested and consist of aminoacids, simple sugars, and
[34, 37]. However, there is still some doubt whether the
enough fat to prevent essential fatty acid deficiency. Semiele-
pancreatic secretion is fully suppressed. Overall, the concept
mental formulas required less digestion than polymeric
of pancreatic rest seems to be less probable.
foods and contain peptides of varying chain length, simple
sugars, glucose polymers, or starch and fat primarily as
medium chain triglycerides. Polymeric feeds contain non-
3. Outcomes of Nutritional Support hydrolyzed proteins, complex carbohydrates, and long chain
triglycerides. Based on the assumption that elemental and
Nutritional therapy in the past has been governed by the
semielemental formulas cause less pancreatic stimulation
principle that the gut should be put at rest with avoidance
than standard formulas, most EN studies have used an
of any stimulation of pancreatic exocrine secretion. These
elemental or a semielemental formula. It would seem that
concepts should now be replaced by the principle that
the location of the enteral tube is just as important as the
pancreatic stimulation should be reduced to basal rates,
type of enteral formulas in stimulating pancreatic secretion.
but that gut integrity should be maintained and that the
Few data exist on the use of standard enteral formula in
stress response should be contained to reduce the likelihood
such patients. Both Windsor et al. and Pupelis et al. have
of multiorgan failure, nosocomial infections, and mortality
shown that polymeric formula can be safely fed through
[38].
jejunal tubes in AP patients [17, 41]. In a longitudinal study
The question remains if nutritional support is beneficial
by Makola et al., 126 patients received standard formula via
for the outcome of AP. Powell et al. published the only ran-
a jejunal tube which was inserted through a percutaneous
domized controlled trial comparing EN with no nutritional
endoscopic gastrostomy (PEG-J) [42]. The standard enteral
support and studied the effect of early EN on the markers of
formula resulted in both a significant decrease of the median
inflammatory response in severe AP [39]. Nutrition therapy
CT severity index and increase of serum albumin compared
provided by the enteral route did not have a more favorable
from baseline to the time of tube removal. Few studies
impact on patient outcome than standard therapy as no
have defined the benefits of semielemental versus polymeric
differences were found between the two groups with respect
formulas in severe AP. In 1989, Cravo et al. found a similar
to overall complications, length of hospital stay, or the time
tolerance in 102 patients with AP given semielemental versus
to resume an oral diet. Serum markers of inflammation
polymeric formulas [43]. Tiengou et al. compared in a
appeared to be lower in the group receiving EN compared
randomized trial semielemental and polymeric formulas in
with those randomized to standard therapy, but none of
30 AP patients [44]. Both formulas were well tolerated
the differences was statistically significant. The findings of
and well absorbed, but the semielemental group had less
this study suggest that low-caloric EN does not modify
weight loss and a shorter length of hospital stay compared
the inflammatory response in severe AP, but limits in the
with the polymeric group. Recently, Petrov et al. conclude
design of the study should be mentioned: only 21% of the
from their adjusted meta-analysis that the use of polymeric,
caloric requirements were infused in the EN group, the study
compared with (semi)elemental formulation, does not lead
duration was only 4 days, and small numbers of patients were
to a significantly higher risk of feeding intolerance, infectious
recruited.
complications, or death in AP patients [45]. It should be
As already mentioned, the pancreas is in a state of
remembered that (semi)elemental feeds are sevenfold as
unresponsiveness during an attack of AP and the secretion
expensive as polymeric feeds. In summary, the evidence base
of pancreatic juice and trypsin is reduced during AP [34,
to just use (semi) elemental formulas becomes less clear.
37]. Eckerwall et al. investigated the role of immediate oral
feeding versus fasting in 60 patients with AP [40]. All patients
received initial aggressive fluid resuscitation to maintain 4.2. Use of Supplements in Enteral Nutrition. Although the
intravascular circulatory volume, microcirculation, and renal use of glutamine supplementation, immunonutrition and
function, thereby minimizing the extent of ischemia and prebiotics, and/or probiotics is conceptually sound and
reperfusion injury. Compared to the fasting patients, the attractive, their use is not supported by large-scale studies
orally fed group had a significantly shorter period of [15, 46, 47].
intravenous fluids, less days of fasting, and a 2-day earlier Two studies evaluated the use of immune-enhancing
introduction of solid foods, with no differences in blood formulas, containing glutamine, arginine and fibers or
4 Gastroenterology Research and Practice
glutamine, arginine, ω-3 fatty acids, vitamins, and micronu-
trients [48, 49]. Hallay et al. compared the effect of a
glutamine-rich with a nonglutamine-rich enteral formula on
immunologic parameters in 16 patients with AP [48]. The
recovery of immunological parameters was better and the
time of disease recovery was shorter in the glutamine-treated
group. Pearce et al. supplemented in a randomised controlled
trial arginine, glutamine, ω-3 fatty acids, and antioxidants in
31 patients with severe AP [49]. Surprisingly, an increase in
CRP was found in the study group compared with the control
group. No significant difference in the length of hospital stay
was observed. Although a lower incidence of pneumonia
and MOF, and shorter length of ICU- and hospital stay
was observed in the immunonutrition group, none of these
differences reached statistical significance.
Lasztity et al. randomly administered ω-3 fatty acids
enterally to 28 patients with moderately severe AP [50].
Supplementation significantly lowered the length of hospital
stay and the duration of nutritional therapy, without a
significant decrease in overall complication rate.
Karakan et al. performed the only study to look at a
possible role of prebiotics in the attenuation of the severity
of AP [51]. They found a significant reduction in hospital
stay and duration of the acute phase response in patients
receiving prebiotics compared with controls. The study
comprised only 30 patients and needs confirmation in larger
series.
Probiotics might prevent infectious complications by
reducing small-bowel bacterial overgrowth, restoring gas-
trointestinal barrier function, and modulating the immune
system [52–54]. Oláh et al. demonstrated that Lactobacillus
plantarum (probiotic) in conjunction with oat fiber (prebi-
otic) was successful in reducing septic complications (4.5%)
versus control (30%) in patients with AP, suggesting that
the probiotic therapy enhances the effect of EN in reducing
infectious morbidity, however, without a difference in length
of hospital stay [55]. Oláh et al. also studied four different
prebiotics and probiotics, contained in Synbiotic 2000, and
found a decrease in inflammatory response and multiorgan
failure in the presence of severe AP [56]. Besselink et al.
performed the only large-scale multicenter randomized trial
in which 298 patients with a predicted severe AP were
randomly assigned to receive a multispecies (Lactobacilli and
Bifidobacterium) probiotic preparation or placebo adminis-
tered enterally [57]. There was no difference in the rate of
infectious complications; however, in the probiotic group,
the incidence of MOF and the mortality (16% versus 6%)
was significantly higher [58]. Nine patients in the probiotics
group developed bowel ischaemia, but none in the placebo
group. The pathophysiological mechanism that explains why
bowel ischaemia developed in patients having had probiotics
is unclear, but based on these unexpected study results
the use of probiotic prophylaxis in patients with predicted
severe AP is highly discouraged. Petrov et al. conclude
in their systematic review that supplementation of EN
with immunonutrition or probiotics does not significantly
improve clinically outcomes and their use is not recom-
mended [45]. Fibre-enriched formulation may be safely
administered, but an adequately powered RCT is warranted.
In conclusion, specific supplements added to EN such
as arginine, glutamine, ω-3 polyunsaturated fatty acids, and
prebiotics may be associated with a positive impact on
outcome, but studies are too few and underpowered to
make strong treatment recommendations [15, 47]. Probi-
otics should not be administered routinely in patients with
predicted severe AP.
5. Timing of Enteral Support
The precise timing for initiating enteral support has not been
specifically addressed in the pancreatitis population but has
been studied to a large extent in the critically ill population.
The delivery of EN to critically ill patients early upon
admission to the ICU alters physiology in a way that down
regulates systemic immunity, reduces overall oxidative stress,
and improves patient outcome [59]. Early EN started prior to
48 hours from admission in critically ill patients is associated
with a significant 24% reduction in infectious complications
and a 32% reduction in mortality compared with delayed
feedings started after that point time [59, 60].
Marik and Zaloga found in their meta-analysis that
“early” EN (within 36 hours) versus delayed EN (after
36 hours) delayed infectious complications and reduced
the length of hospital stay in head injury, trauma, burns,
postoperative and medical ICU patients [61]. However,
caution must be exercised when making inferences about
patients with pancreatitis based on information that is
gathered from the critically ill.
Recently, Petrov et al. conducted a systematic review of
randomized controlled trials on the effect of EN versus TPN
in patients with mild and severe AP with regard to the timing
of nutrition support [13]. EN started within 48 hours of
admission resulted in a significant reduction in multiorgan
failure, pancreatic infectious complications, and mortality.
These significant differences between EN versus TPN faded
away when nutrition support started after 48 hours of
admission. So EN started within 48 hours of admission may
be beneficial and a randomized controlled trial, which has
been started, may give a more definite answer.
6. Route of Enteral Nutrition Support and
Tolerance of Enteral Feeding
Per oral ingestion of nutrients is often hampered by abdom-
inal pain with food aversion, nausea, vomiting, gastric atony,
and paralytic ileus or by partial duodenal obstruction from
pancreatic gland enlargement [19]. The application of early
EN may be limited by the severity of the pancreatitis attack
and the occurrence of ileus.
Traditionally, AP management involved fasting the
patient until resolution of symptoms. Recent work has
suggested that EN via a jejunal tube is safe and may increase
antioxidant activity and reduce the acute phase response and
the magnitude of the inflammatory response [17].
Most of the feeding tubes are placed as nasojejunal tubes
using an endoscopic or a radiologic procedure. Alternatively,
Gastroenterology Research and Practice
especially if the expected period of feeding is 4–6 weeks or
more, laparoscopic or radiologic jejunal feeding tubes can
be placed. Tolerance is defined by the provision of adequate
feeding without ill effects. Tolerance is primary determined
by the balance between feeding into the gastrointestinal
tract which can be in a state of partial ileus and providing
enteral nutrients while causing only minimal stimulation
of pancreatic exocrine secretion. Therefore, patients with
nasointestinal tubes placed at or below the ligament of Treitz
should be monitored very closely for evidence of tube migra-
tion as well as evidence of intolerance such as high residual
volume, nausea and vomiting, diarrhea, or aspiration of
feeding formula. A wide range of tolerance to EN exists
irrespective of known influences such as mode (continuous
or bolus) and level of infusion within the gastrointestinal
tract (gastric versus postpyloric). In patients operated on
for complications of AP, continuous infusion appeared to be
safer and reduced the stimulation of the pancreas better than
bolus infusion [62]. However, insufficient data do not allow
a determination of whether continuous or bolus infusion is
superior.
After a feasibility study, Eatock et al. performed a
randomized controlled study of early nasogastric versus
nasojejunal feeding in severe AP [63, 64]. They discovered
a surprising tolerance to nasogastric feeding and recom-
mended that nasogastric feeding should be considered a
therapeutic option because of its simplicity, obviating the
need for endoscopic, radiologic procedures. Eatock’s study,
however, had several limitations, one of them being the
failure to fluoroscopically confirm that the nasojejunal tubes
were appropriately positioned in the jejunum. There is no
indication whether the nasojejunal tubes were placed distal
enough (at least 60 cm from the ligament of Treitz) to avoid
gastric and pancreatic stimulation. The failure to find a
difference may have been related to continued gastric and
duodenal stimulation occurring in both groups of patients.
Similar findings from randomized studies were reported by
Kumar et al. (nasogastric versus nasojejunal) and Eckerwall
et al. (nasogastric versus TPN) [65, 66].
Jiang et al. included the 3 RCTs, involving 131 patients, in
a meta-analysis [32]. The primary outcome of effectiveness
was overall mortality, secondary outcomes of effectiveness
were hospital stay, complications and their management.
Outcome measure of safety was the occurrence of pain on
refeeding and adverse events related to nasogastric EN. The
comparator intervention was early EN through a nasogastric
tube, the control intervention was one of the conventional
pancreatic-rest nutritional support routes of total parenteral
or intrajejunal feeding. The meta-analysis showed no signif-
icant differences in mortality rate between nasogastric and
conventional routes (nasojejunal and parenteral feeding).
Also, other outcomes were not different such as length of
hospital stay, infectious complications, multiorgan failure,
rate of admissions to the ICU, or conversion to surgery.
Also, the recurrence of pain on refeeding and adverse events
associated with nutrition were similar.
Petrov et al. performed an extended systematic review
which included the 3 RCTs included in the Jiang meta-
analysis and the study of Eatock [33]. They also concluded
5
that nasogastric feeding appeared to be safe and well
tolerated in the majority (79%) of patients. The aggregated
data from the two RCTs comparing nasogastric to nasoje-
junal feeding showed no statistically significant difference
in mortality and tolerance. Both meta-analyses conclude
that a well-powered randomized trial on nasogastric versus
nasojejunal feeding is indicated to provide a more firm
and conclusive evidence to recommend nasogastric feeding
as routine clinical practice in patient with acute pancreati-
tis.
7. Timing and Nutrient Composition of
Oral Support
Data about when to resume oral feeding in patients with
acute pancreatitis or the optimal nutrient composition are
scare [40, 67, 68]. The usual criteria to initiate oral feeding
are (1) absence of abdominal pain, (2) absence of nausea
and vomiting, and return of appetite, and (3) absence of
complications. It is possible that the recurrence of pain
during the reintroduction of the oral diet is related to
ingestion of larger volumes rather than to ongoing or
renewed intrapancreatic release of enzymes [64]. Usually,
patients are refed small amounts of food frequently during
the day and the total number of daily calories is gradually
increased over a three- to six-day period [69]. Therefore,
feeding is often begun using a clear liquid, a diet for the
first 24 hours. If tolerated the diet is advanced to soft
low-fat diet over the next 24 hour and then to a low fat
solid diet. No clinical trials evaluating these routines are
available. A low-fat diet is advised when oral intake is
resumed in patients recovering from AP. This is based on
the observation that intraduodenal lipids increase volume,
bicarbonate, trypsin, and amylase output in volunteers [70].
Besides the presumed stimulation of pancreas exocrine
secretion by fat, there might be another reason to postpone
fat intake. Pancreatic lipase is less stable than other pancreatic
enzymes against acid denaturation and destruction by pepsin
and pancreatic proteases, in particularly by chymotrypsin
present in chime. This may render lipid digestion more
vulnerable in pathologic conditions [71, 72]. Trypsin is not
inactivated by acid but only by pepsin.
Tolerance to advancement to oral diets was evaluated
in 274 patients at the point at which abdominal pain
had resolved and ileus had subsided [73]. Sixty patients
(21.9%) experienced pain relapse and 47 of these 60 subjects
pain relapsed within 48 hours of commencement of oral
feeding. No pain relapse or pain occurred in those patients
randomized to jejunal tube feedings, started a median of
7 days after the onset of symptoms [74]. However, in 4 of
the 15 patients (27%) randomized to oral bolus feedings
after a median of 5 days after the onset of symptoms, pain
on refeeding was associated with longer duration of initial
pain and a higher severity index on CT. Lévy et al. came
to the same conclusion in a large number of 116 patients
[69]. According to the Ranson score ≥3, 35% had a severe
AP, and according to the Balthazar CT score >D, this was
the case in 42% of patients. Twenty-one per cent of patients
6 Gastroenterology Research and Practice
had a relapse of pain. The risk of pain relapse increased if
serum lipase was greater than three times normal the day
before the start of feeding, and was higher in patients who
had a longer duration of pain (11 days versus 6 days) and in
patients who had a worse CT score (Balthazar score greater
than D). The exacerbation of symptoms resulted in doubling
of the length of stay in hospital (from 18 to 33 days). Chebli et
al. found a similar number of days of abdominal pain before
oral refeeding in those that did and did not relapse [75].
Pain relapse was predicted by peripancreatic fluid collection,
serum CRP on the 4th day, and serum lipase on the day of
oral feeding.
Jacobson et al. hypothesized that patients recovering
from mild AP would be discharged from the hospital
sooner if they resumed oral nutrition with a low-fat solid
diet compared with a clear liquid diet [67]. Patients with
mild pancreatitis were randomized to a clear liquid diet
or low-fat solid diet when they were ready to resume oral
nutrition. Patients were monitored daily for recurrence of
pain, need to stop feeding, post-refeeding length of hospital
stay (primary endpoint), and for 28 days post-refeeding to
capture readmission rates. 1335 patients were assessed for
eligibility and 66 allocated to a clear liquid diet (588 kcal,
2 g fat) and 55 to a low fat solid diet (1200 kcal, 35 g fat).
Because of the large number of excluded patients, a bias
by selection may have occurred. The number of patients
requiring cessation of feeding because of pain or nausea was
similar (6% and 11%, resp.), the median length of stay after
refeeding was similar, and there was no difference in the 28-
day readmission rates. Patients on the low fat diet consumed
significantly more calories and grams of fat during their
first meal and on study day 1 (301 kcal and 2 g fat versus
622 kcal and 13 g fat, P < .001). Initiating oral nutrition
after mild pancreatitis with a low fat solid diet appeared to
be safe and provided more calories than a clear liquid diet,
but did not result in a shorter length of hospitalization. The
abdominal pain score on the day of refeeding was associated
with a failure of oral intake with those experiencing more
pain having a higher likelihood of being made nil per mouth.
Unfortunately, the authors failed to resolve the important
question of what the optimal diet should be in patients
recovering from mild pancreatitis. Sathiaraj et al. performed
a randomized trial to determine the length of hospital stay
and tolerance to oral refeeding in patients with mild AP and
acute on chronic pancreatitis when started on a soft diet (n =
52, 1040 kcal and 20 g fat) as compared to a clear liquid diet
(n = 49, 458 kcal and 11 g fat) [68]. The length of hospital
stay (post-refeeding and total) decreased significantly on a
soft diet. They observed no significant difference in the need
for cessation of feeding because of pain or nausea. Patients on
the soft diet consumed significantly more calories and grams
of fat during their first meal and on study day 1 (921 kcal and
15 g fat versus 370 kcal and 8 g fat, P < .001). They concluded
that oral refeeding with a soft diet was safe and resulted in a
shorter length of hospital stay. However, in both nonblinded
studies, a definition of when to discharge patients was not
given. Hospital discharge was decided by the medical team
without input from study team.
8. Guidelines of Enteral Nutrition in
Acute Pancreatitis
Recently, several general practice guidelines for AP have been
published [1, 4, 8, 76–78]. These comment on nutritional
management in mild and severe AP. The European Society
of Parenteral and Enteral Nutrition (ESPEN) published
a revised and comprehensive guideline on EN in AP in
2006 [8]. The several guidelines cover mostly the same
recommendations. To date some of the recommendations
require updating according to the best available evidence as
discussed above. Generally, for mild AP it is recommend to
initiate EN if patients cannot consume normal food after 5–7
days. For severe AP nutritional support is indicated when it
becomes evident that the patient will not be able to tolerate
oral intake for a prolonged period of time, for example, for
at least 7 days. This assessment can usually be made within
the first 3-4 days of admission. EN should be supplemented
by parenteral nutrition if needed. Also, in severe pancreatitis
with complications such as pancreatic fistulas, ascites, and
pseudocysts, tube feeding can be given uneventfully. If gastric
feeding is not tolerated, the jejunal route should be tried and
continuous feeding in stead of bolus feeding should be used.
In gastric outlet obstruction, feeding beyond the obstruction
with the tube tip distal to the obstruction should be tried.
If this is impossible, parenteral nutrition should be given.
In case of surgery for complications of AP, an intraoperative
jejunostomy for postoperative feeding is feasible.
Peptid-based semielemental formulas can be used safely
and standard formulae can be tried if they are tolerated.
9. Summary of Recent Developments
Most patients with AP have mild disease and do not need
additional nutritional support during admission. According
to the guidelines, nutritional support is indicated if patients
cannot consume normal food after 5–7 days or when it
becomes evident that the patient will not be able to tolerate
oral intake for a prolonged period of time (7 days or more).
When artificial nutrition is indicated, EN is preferred over
TPN, because it reduces complications and mortality in AP
when compared with TPN. TPN should only be used in
patients unable to tolerate EN. It is likely that EN has a bene-
ficial influence on the disease course and should be initiated
as early as possible (within 48 hours of admission). With
some caution it can be stated that nasogastric tube feeding in
severe AP is possible, making the concept of pancreatic rest
less probable. However, larger multicentre studies are needed
to confirm the safety and effectiveness of nasogastric feeding
when compared to nasojejunal feeding and to investigate
the role of early (within 48 hours) versus late nutrition
support. Randomized controlled trails have been started
and will hopefully give a more definite answer. The clinical
evidence for the use of just (semi) elemental formulas is
weak. Supplementation of enteral formulas with glutamine
and prebiotics and the use of immune enhancing formulas
cannot routinely be recommended. Probiotics should not be
administered routinely in patients with predicted severe AP.
Gastroenterology Research and Practice 7

To date, some of the recommendations as stated in the latest [11] P. E. Marik and G. P. Zaloga, “Meta-analysis of parenteral-
guidelines require updating according to the best available nutrition versus enteral nutrition in patients with acute
evidence. pancreatitis,” British Medical Journal, vol. 328, no. 7453, pp.
1407–1410, 2004.
[12] S. A. McClave, W.-K. Chang, R. Dhaliwal, and D. K. Heyland,
Abbreviations “Nutrition support in acute pancreatitis: a systematic review
AP: Acute pancreatitis of the literature,” Journal of Parenteral and Enteral Nutrition,
vol. 30, no. 2, pp. 143–156, 2006.
NPO: Nil per os
[13] M. S. Petrov, R. D. Pylypchuk, and A. F. Uchugina, “A
EN: Enteral nutrition
systematic review on the timing of artificial nutrition in acute
TPN: Total parenteral nutrition pancreatitis,” British Journal of Nutrition, vol. 19, pp. 1–7,
SIRS: Systemic inflammatory response syndrome 2008.
MOF: Multiorgan failure [14] M. S. Petrov, H. C. van Santvoort, M. G. H. Besselink, G. J.
ICU: Intensive care unit M. G. van Der Heijden, J. A. Windsor, and H. G. Gooszen,
RCT: Randomized controlled trial “Enteral nutrition and the risk of mortality and infectious
CCK: Cholecystokin complications in patients with severe acute pancreatitis: a
VIP: Vasoactive intestinal peptide. meta-analysis of randomized trials,” Archives of Surgery, vol.
143, no. 11, pp. 1111–1117, 2008.
[15] P. E. Marik, “What is the best way to feed patients with
Acknowledgment pancreatitis?” Current Opinion in Critical Care, vol. 15, no. 2,
B. W. M. Spanier is sponsored by an unrestricted grand from pp. 131–138, 2009.
Axcan Pharma Incorporate, Canada. [16] B. J. Ammori, “Role of the gut in the course of severe acute
pancreatitis,” Pancreas, vol. 26, no. 2, pp. 122–129, 2003.
[17] A. C. J. Windsor, S. Kanwar, A. G. K. Li et al., “Compared with
Competing Interest parenteral nutrition, enteral feeding attenuates the acute phase
response and improves disease severity in acute pancreatitis,”
The author declared that there is no competing interest. Gut, vol. 42, no. 3, pp. 431–435, 1998.
[18] H. G. Beger and B. M. Rau, “Severe acute pancreatitis: clinical
References course and management,” World Journal of Gastroenterology,
vol. 13, no. 38, pp. 5043–5051, 2007.
[1] P. A. Banks, M. L. Freeman, R. Fass et al., “Practice guidelines [19] S. A. McClave, H. Snider, N. Owens, and L. K. Sexton, “Clinical
in acute pancreatitis,” American Journal of Gastroenterology, nutrition in pancreatitis,” Digestive Diseases and Sciences, vol.
vol. 101, no. 10, pp. 2379–2400, 2006. 42, no. 10, pp. 2035–2044, 1997.
[2] S. J. Pandol, A. K. Saluja, C. W. Imrie, and P. A. Banks, “Acute [20] H. Ragins, S. M. Levenson, and R. Signer, “Intrajejunal
pancreatitis: bench to the bedside,” Gastroenterology, vol. 132, administration of an elemental diet at neutral pH avoids
no. 3, pp. 1127–1151, 2007. pancreatic stimulation: studies in dog and man,” American
[3] B. W. M. Spanier, M. G. W. Dijkgraaf, and M. J. Bruno, Journal of Surgery, vol. 126, no. 5, pp. 606–614, 1973.
“Epidemiology, aetiology and outcome of acute and chronic [21] S. Marulendra and D. F. Kirby, “Nutrition support in pancre-
pancreatitis: an update,” Best Practice and Research in Clinical atitis,” Nutrition in Clinical Practice, vol. 10, no. 2, pp. 45–53,
Gastroenterology, vol. 22, no. 1, pp. 45–63, 2008. 1995.
[4] C. E. Forsmark and J. Baillie, “AGA Institute technical review [22] S. A. Mcclave, L. M. Greene, H. L. Snider et al., “Comparison
on acute pancreatitis,” Gastroenterology, vol. 132, no. 5, pp. of the safety of early enteral vs parenteral nutrition in mild
2022–2044, 2007. acute pancreatitis,” Journal of Parenteral and Enteral Nutrition,
[5] M. S. Petrov, R. D. Pylypchuk, and N. V. Emelyanov, vol. 21, no. 1, pp. 14–20, 1997.
“Systematic review: nutritional support in acute pancreatitis,”
[23] R. Meier, C. Beglinger, P. Layer et al., “ESPEN guidelines on
Alimentary Pharmacology and Therapeutics, vol. 28, no. 6, pp.
nutrition in acute pancreatitis,” Clinical Nutrition, vol. 21, no.
704–712, 2008.
2, pp. 173–183, 2002.
[6] O. Ioannidis, A. Lavrentieva, and D. Botsios, “Nutrition
support in acute pancreatitis,” Journal of the Pancreas, vol. 9, [24] R. F. Meier and C. Beglinger, “Nutrition in pancreatic
no. 4, pp. 375–390, 2008. diseases,” Best Practice & Research: Clinical Gastroenterology,
[7] R. Talukdar and S. S. Vege, “Recent developments in acute vol. 20, no. 3, pp. 507–529, 2006.
pancreatitis,” Clinical Gastroenterology and Hepatology, vol. 7, [25] S. J. D. O’Keefe, R. B. Lee, F. P. Anderson et al., “Physiological
pp. S3–S9, 2009. effects of enteral and parenteral feeding on pancreaticobil-
[8] R. Meier, J. Ockenga, M. Pertkiewicz et al., “ESPEN guidelines iary secretion in humans,” American Journal of Physiology—
on enteral nutrition: pancreas,” Clinical Nutrition, vol. 25, no. Gastrointestinal and Liver Physiology, vol. 284, no. 1, pp. G27–
2, pp. 275–284, 2006. G36, 2003.
[9] L. Gianotti, R. Meier, D. N. Lobo et al., “ESPEN guidelines on [26] S. J. D. O’Keefe, R. B. Lee, J. Li, W. Zhou, B. Stoll, and Q. Dang,
parenteral nutrition: pancreas,” Clinical Nutrition, vol. 28, no. “Trypsin and splanchnic protein turnover during feeding and
4, pp. 428–435, 2009. fasting in human subjects,” American Journal of Physiology—
[10] R. L. Koretz, A. Avenell, T. O. Lipman, C. L. Braunschweig, and Gastrointestinal and Liver Physiology, vol. 290, no. 2, pp. G213–
A. C. Milne, “Does enteral nutrition affect clinical outcome? A G221, 2006.
systematic review of the randomized trials,” American Journal [27] S. Abou-Assi, K. Craig, and S. J. D. O’Keefe, “Hypocaloric
of Gastroenterology, vol. 102, no. 2, pp. 412–429, 2007. jejunal feeding is better than total parenteral nutrition in
8 Gastroenterology Research and Practice
acute pancreatitis: results of a randomized comparative study,”
American Journal of Gastroenterology, vol. 97, no. 9, pp. 2255–
2262, 2002.
[28] M. K. Russell, “Acute pancreatitis: a review of pathophysiology
and nutrition management,” Nutrition in Clinical Practice, vol.
19, no. 1, pp. 16–24, 2004.
[29] J. S. Scolapio, N. Malhi-Chowla, and A. Ukleja, “Nutrition
supplementation in patients with acute and chronic pancre-
atitis,” Gastroenterology Clinics of North America, vol. 28, no.
3, pp. 695–707, 1999.
[30] M. K. Vu, P. P. J. Van Der Veek, M. Frölich et al., “Does jejunal
feeding activate exocrine pancreatic secretion?” European
Journal of Clinical Investigation, vol. 29, no. 12, pp. 1053–1059,
1999.
[31] N. Kaushik, M. Pietraszewski, J. J. Holst, and S. J. D. O’Keefe,
“Enteral feeding without pancreatic stimulation,” Pancreas,
vol. 31, no. 4, pp. 353–359, 2005.
[32] K. Jiang, X.-Z. Chen, Q. Xia, W.-F. Tang, and L. Wang, “Early
nasogastric enteral nutrition for severe acute pancreatitis: a
systematic review,” World Journal of Gastroenterology, vol. 13,
no. 39, pp. 5253–5260, 2007.
[33] M. S. Petrov, M. I. T. D. Correia, and J. A. Windsor, “Naso-
gastric tube feeding in predicted severe acute pancreatitis. A
systematic review of the literature to determine safety and
tolerance,” Journal of the Pancreas, vol. 9, no. 4, pp. 440–448,
2008.
[34] C. Niederau, M. Niederau, R. Luthen, G. Strohmeyer, L. D.
Ferrell, and J. H. Grendell, “Pancreatic exocrine secretion in
acute experimental pancreatitis,” Gastroenterology, vol. 99, no.
4, pp. 1120–1127, 1990.
[35] B. Boreham and B. J. Ammori, “A prospective evaluation
of pancreatic exocrine function in patients with acute pan-
creatitis: correlation with extent of necrosis and pancreatic
endocrine insufficiency,” Pancreatology, vol. 3, no. 4, pp. 303–
308, 2003.
[36] S. J. D. O’Keefe, R. B. Lee, J. Li, S. Stevens, S. Abou-Assi, and W.
Zhou, “Trypsin secretion and turnover in patients with acute
pancreatitis,” American Journal of Physiology—Gastrointestinal
and Liver Physiology, vol. 289, no. 2, pp. G181–G187, 2005.
[37] S. J. O’Keefe and S. A. McClave, “Feeding the injured
pancreas,” Gastroenterology, vol. 129, no. 3, pp. 1129–1130,
2005.
[38] S. A. McClave, D. A. Spain, and H. L. Snider, “Nutritional
management in acute and chronic pancreatitis,” Gastroenterol-
ogy Clinics of North America, vol. 27, no. 2, pp. 421–434, 1998.
[39] J. J. Powell, J. T. Murchison, K. C. H. Fearon, J. A. Ross, and
A. K. Siriwardena, “Randomized controlled trial of the effect
of early enteral nutrition on markers of the inflammatory
response in predicted severe acute pancreatitis,” British Journal
of Surgery, vol. 87, no. 10, pp. 1375–1381, 2000.
[40] G. E. Eckerwall, B. B. A. Tingstedt, P. E. Bergenzaun, and
R. G. Andersson, “Immediate oral feeding in patients with
mild acute pancreatitis is safe and may accelerate recovery-A
randomized clinical study,” Clinical Nutrition, vol. 26, no. 6,
pp. 758–763, 2007.
[41] G. Pupelis, G. Selga, E. Austrums, and A. Kaminski, “Jejunal
feeding, even when instituted late, improves outcomes in
patients with severe pancreatitis and peritonitis,” Nutrition,
vol. 17, no. 2, pp. 91–94, 2001.
[42] D. Makola, J. Krenitsky, C. Parrish et al., “Efficacy of enteral
nutrition for the treatment of pancreatitis using standard
enteral formula,” American Journal of Gastroenterology, vol.
101, no. 10, pp. 2347–2355, 2006.
[43] M. Cravo, M. E. Camilo, A. Marques, and J. Correia, “Early
tube feeding in acute pancreatitis: a prospective study,” Clinical
Nutrition, pp. A8–A14.
[44] L.-E. Tiengou, R. Gloro, J. Pouzoulet et al., “Semi-elemental
formula or polymeric formula: is there a better choice for
enteral nutrition in acute pancreatitis? Randomized compar-
ative study,” Journal of Parenteral and Enteral Nutrition, vol.
30, no. 1, pp. 1–5, 2006.
[45] M. S. Petrov, B. P. T. Loveday, R. D. Pylypchuk, K. McIlroy,
A. R. J. Phillips, and J. A. Windsor, “Systematic review
and meta-analysis of enteral nutrition formulations in acute
pancreatitis,” British Journal of Surgery, vol. 96, no. 11, pp.
1243–1252, 2009.
[46] A. Kingsnorth and D. O’Reilly, “Acute pancreatitis,” British
Medical Journal, vol. 332, no. 7549, pp. 1072–1076, 2006.
[47] A. Thomson, “Nutritional support in acute pancreatitis,”
Current Opinion in Clinical Nutrition and Metabolic Care, vol.
11, no. 3, pp. 261–266, 2008.
[48] J. Hallay, G. Kovács, K. Szatmári et al., “Early jejunal nutrition
and changes in the immunological parameters of patients with
acute pancreatitis,” Hepatogastroenterology, vol. 48, no. 41, pp.
1488–1492, 2001.
[49] C. B. Pearce, S. A. Sadek, A. M. Walters et al., “A double-blind,
randomised, controlled trial to study the effects of an enteral
feed supplemented with glutamine, arginine, and omega-3
fatty acid in predicted acute severe pancreatitis,” Journal of the
Pancreas, vol. 7, no. 4, pp. 361–371, 2006.
[50] N. Lasztity, J. Hamvas, L. Biró et al., “Effect of enterally admin-
istered n-3 polyunsaturated fatty acids in acute pancreatitis—a
prospective randomized clinical trial,” Clinical Nutrition, vol.
24, no. 2, pp. 198–205, 2005.
[51] T. Karakan, M. Ergun, I. Dogan, M. Cindoruk, and S.
Unal, “Comparison of early enteral nutrition in severe acute
pancreatitis with prebiotic fiber supplementation versus stan-
dard enteral solution: a prospective randomized double-blind
study,” World Journal of Gastroenterology, vol. 13, no. 19, pp.
2733–2737, 2007.
[52] S. Bengmark, “Bio-ecological control of acute pancreatitis: the
role of enteral nutrition, pro and synbiotics,” Current Opinion
in Clinical Nutrition and Metabolic Care, vol. 8, no. 5, pp. 557–
561, 2005.
[53] S. Bengmark, “Ecological control of the gastrointestinal tract.
The role of probiotic flora,” Gut, vol. 42, no. 1, pp. 2–7, 1998.
[54] F. Guarner and J.-R. Malagelada, “Gut flora in health and
disease,” The Lancet, vol. 361, no. 9356, pp. 512–519, 2003.
[55] A. Oláh, T. Belágyi, Á. Issekutz, M. E. Gamal, and S.
Bengmark, “Randomized clinical trial of specific lactobacillus
and fibre supplement to early enteral nutrition in patients with
acute pancreatitis,” British Journal of Surgery, vol. 89, no. 9, pp.
1103–1107, 2002.
[56] A. Oláh, T. Belágyi, L. Pótó, L. Romics Jr., and S. Bengmark,
“Synbiotic control of inflammation and infection in severe
acute pancreatitis: a prospective, randomized, double blind
study,” Hepatogastroenterology, vol. 54, no. 74, pp. 590–594,
2007.
[57] M. G. Besselink, H. C. van Santvoort, E. Buskens et al.,
“Probiotic prophylaxis in predicted severe acute pancreatitis:
a randomised, double-blind, placebo-controlled trial,” The
Lancet, vol. 371, no. 9613, pp. 651–659, 2008.
[58] S. A. McClave, D. K. Heyland, and P. E. Wischmeyer,
“Probiotic prophylaxis in predicted severe acute pancreatitis:
a randomized, double-blind, placebo-controlled trial,” Journal
of Parenteral and Enteral Nutrition, vol. 33, no. 4, pp. 444–446,
2009.
Gastroenterology Research and Practice 9

[59] S. A. McClave and D. K. Heyland, “The physiologic response [75] J. M. F. Chebli, P. D. Gaburri, A. F. M. De Souza et al., “Oral
and associated clinical benefits from provision of early enteral refeeding in patients with mild acute pancreatitis: prevalence
nutrition,” Nutrition in Clinical Practice, vol. 24, no. 3, pp. and risk factors of relapsing abdominal pain,” Journal of
305–315, 2009. Gastroenterology and Hepatology, vol. 20, no. 9, pp. 1385–1389,
[60] D. K. Heyland, R. Dhaliwal, J. W. Drover, L. Gramlich, and 2005.
P. Dodek, “Canadian clinical practice guidelines for nutrition [76] C. D. Johnson, “UK guidelines for the management of acute
support in mechanically ventilated, critically ill adult patients,” pancreatitis,” Gut, vol. 54, supplement 3, pp. iii1–iii9, 2005.
Journal of Parenteral and Enteral Nutrition, vol. 27, no. 5, pp. [77] J. Baillie, “AGA Institute medical position statement on acute
355–373, 2003. pancreatitis,” Gastroenterology, vol. 132, no. 5, pp. 2019–2021,
[61] P. E. Marik and G. P. Zaloga, “Early enteral nutrition in acutely 2007.
ill patients: a systematic review,” Critical Care Medicine, vol. [78] J. Toouli, M. Brooke-Smith, C. Bassi et al., “Guidelines for the
29, no. 12, pp. 2264–2270, 2001. management of acute pancreatitis,” Journal of Gastroenterology
[62] L. Harsányi, G. Bodoky, and A. Pap, “The effect of jejunal and Hepatology, vol. 17, no. 1, pp. S15–S39, 2002.
nutrition on pancreatic exocrine function,” Acta Chirurgica
Hungarica, vol. 33, no. 1-2, pp. 13–21, 1992.
[63] F. C. Eatock, G. D. Brombacher, A. Steven, C. W. Imrie, C.
J. McKay, and R. Carter, “Nasogastric feeding in severe acute
pancreatitis may be practical and safe,” International Journal of
Pancreatology, vol. 28, no. 1, pp. 23–29, 2000.
[64] F. C. Eatock, P. Chong, N. Menezes et al., “A randomized study
of early nasogastric versus nasojejunal feeding in severe acute
pancreatitis,” American Journal of Gastroenterology, vol. 100,
no. 2, pp. 432–439, 2005.
[65] G. E. Eckerwall, J. B. Axelsson, and R. G. Andersson, “Early
nasogastric feeding in predicted severe acute pancreatitis: a
clinical, randomized study,” Annals of Surgery, vol. 244, no. 6,
pp. 959–965, 2006.
[66] A. Kumar, N. Singh, S. Prakash, A. Saraya, and Y. K. Joshi,
“Early enteral nutrition in severe acute pancreatitis: a prospec-
tive randomized controlled trial comparing nasojejunal and
nasogastric routes,” Journal of Clinical Gastroenterology, vol.
40, no. 5, pp. 431–434, 2006.
[67] B. C. Jacobson, M. B. Vander Vliet, M. D. Hughes, R. Maurer,
K. McManus, and P. A. Banks, “A prospective, randomized
trial of clear liquids versus low-fat solid diet as the initial
meal in mild acute pancreatitis,” Clinical Gastroenterology and
Hepatology, vol. 5, no. 8, pp. 946–951, 2007.
[68] E. Sathiaraj, S. Murthy, M. J. Mansard, G. V. Rao, S. Mahukar,
and D. N. Reddy, “Clinical trial: oral feeding with a soft diet
compared with clear liquid diet as initial meal in mild acute
pancreatitis,” Alimentary Pharmacology and Therapeutics, vol.
28, no. 6, pp. 777–781, 2008.
[69] P. Lévy, D. Heresbach, E. A. Pariente et al., “Frequency and
risk factors of recurrent pain during refeeding in patients
with acute pancreatitis: a multivariate multicentre prospective
study of 116 patients,” Gut, vol. 40, no. 2, pp. 262–266, 1997.
[70] P. W. T. Pisters and J. H. C. Ranson, “Nutritional support for
acute pancreatitis,” Surgery Gynecology and Obstetrics, vol. 175,
no. 3, pp. 275–284, 1992.
[71] P. G. Lankisch and W. Creutzfeldt, “Therapy of exocrine and
endocrine pancreatic insufficiency,” Clinics in Gastroenterol-
ogy, vol. 13, no. 3, pp. 985–999, 1984.
[72] R. Meier, “Enteral fish oil in acute pancreatitis,” Clinical
Nutrition, vol. 24, no. 2, pp. 169–171, 2005.
[73] M. S. Petrov, H. C. Van Santvoort, M. G. H. Besselink, G. A.
Cirkel, M. A. Brink, and H. G. Gooszen, “Oral refeeding after
onset of acute pancreatitis: a review of literature,” American
Journal of Gastroenterology, vol. 102, no. 9, pp. 2079–2084,
2007.
[74] S. K. Pandey, V. Ahuja, Y. K. Joshi, and M. P. Sharma, “A
randomized trial of oral refeeding compared with jejunal tube
refeeding in acute pancreatitis,” Indian Journal of Gastroen-
terology, vol. 23, no. 2, pp. 53–55, 2004.